The Fv-1b gene in BALB/c mice inhibits the N-tropic helper virus that naturally accompanies Friend spleen focus-forming virus (SFFV) so that other murine leukemia viruses can substitute as helpers for SFFV. Helper factors for SFFV have also been isolated from cell-free extracts of human leukemic spleen, mycoplasmata, and several species of bacteria. Because helper factors are effective only when injected with SFFV into mice which restrict its helper virus, they resemble helper viruses rather than immunodepressants or target cell stimulators. However, helper factors differ from murine helper viruses by their inability to replicate in neonatal mice and by their greater stability to heat. Although the human leukemic helper (HuLH) extracts examined lack detectable mycoplasma or bacterial contamination, the helper assay in mice will be of limited value as a possible detection system for human leukemogenic viruses until a unique marker is found by which to distinguish HuLH activity from that of prokaryotic origin. This makes a systematic comparison among the non-viral helper factors all the more important.